Effects of exercise training on outcomes inwomen with heart failure. Analysis of HF-ACTION (Heart failure-a controlled trialinvestigating outcomes of exercise training) by Sex

Objectives: The authors hypothesized that the women enrolled in the HF-ACTION (Heart Failure-A Controlled Trial Investigating Outcomes of Exercise TraiNing) trial and randomly assigned to exercise training (ET) would improve functional capacity as measured by peak oxygen uptake (VO₂) compared with those in the usual care group. Furthermore, they hypothesized that the improvement in peak VO₂ would correlate with prognosis. They explored whether exercise had a differential effect on outcomes in women versus men. Background: There is less evidence for the benefit of ET in women with heart failure (HF) compared with men because of the small numbers of women studied. Methods: HF-ACTION was a randomized trial of ET versus usual care in 2,331 patients with class II-IV HF and a left ventricular ejection fraction of≤35%. Sex differences in the effects of randomized treatment on clinical outcomes were assessed through the use of a series of Cox proportional hazards models, controlling for covariates known to affect prognosis in HF-ACTION. Results: Women had lower baseline peak VO₂ and 6-min walk distance than did men (median, 13.4 vs. 14.9 ml/min/kg and 353 vs. 378 m, respectively). An increase in peak VO₂ at 3 months was present in women and men in the ET group (mean ± SD; median, 0.88 ± 2.2, 0.80 and 0.77 ± 2.7, 0.60, respectively, women vs. men; p= 0.42). Women randomly assigned to ET had a significant reduction in the primary endpoint, (hazard ratio: 0.74) compared with men (hazard ratio: 0.99) randomly assigned to ET, with a significant treatment-by-sex interaction (p= 0.027). Conclusions: Although there is no significant difference between men and women in the effect of ET on peak VO₂ change at 3months, ET in women with HF is associated with a larger reduction in rate of the combined endpoint of all-cause mortality and hospital stay than in men.